ArticlePharmaceutical research2005
Quantitative assessment of HIV-1 protease inhibitor interactions with drug efflux transporters in the blood-brain barrier.
Article in Pharmaceutical research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 69 citations in OpenAlex.
- Darunavir concentration in PBMCs may be a better indicator of drug exposure in HIV patients.European journal of clinical pharmacology · 2018Trial
- Mechanism of ritonavir changes in methadone pharmacokinetics and pharmacodynamics: I. Evidence against CYP3A mediation of methadone clearance.Clinical pharmacology and therapeutics · 2008Trial
- Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.International journal of molecular sciences · 2023Review
- Nose to brain delivery of antiretroviral drugs in the treatment of neuroAIDS.Molecular biomedicine · 2020Review
- New ABCC2 rs3740066 and rs2273697 Polymorphisms Identified in a Healthy Colombian Cohort.Pharmaceutics · 2018Article
- Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux?Pharmaceutics · 2018Review
- Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals.AIDS research and treatment · 2016Review
- Role of MRP transporters in regulating antimicrobial drug inefficacy and oxidative stress-induced pathogenesis during HIV-1 and TB infections.Frontiers in microbiology · 2015Review
- Antiretroviral protease inhibitors accelerate glutathione export from viable cultured rat neurons.Neurochemical research · 2014Article
- Darunavir is predominantly unbound to protein in cerebrospinal fluid and concentrations exceed the wild-type HIV-1 median 90% inhibitory concentration.The Journal of antimicrobial chemotherapy · 2013Article
- Examination of blood-brain barrier (BBB) integrity in a mouse brain tumor model.Journal of neuro-oncology · 2013Article
- Therapeutic amprenavir concentrations in cerebrospinal fluid.Antimicrobial agents and chemotherapy · 2012Article
- Lack of indinavir effects on methadone disposition despite inhibition of hepatic and intestinal cytochrome P4503A (CYP3A).Anesthesiology · 2012Article
- Assessment of P-glycoprotein activity in the Blood-Brain Barrier (BBB) using Near Infrared Fluorescence (NIRF) imaging techniques.Pharmaceutical research · 2011Article
- Influence of drug transport proteins on the pharmacokinetics and drug interactions of HIV protease inhibitors.Journal of pharmaceutical sciences · 2011Review
- The transport of anti-HIV drugs across blood-CNS interfaces: summary of current knowledge and recommendations for further research.Antiviral research · 2009Review
- The ART of HIV therapies: dopaminergic deficits and future treatments for HIV pediatric encephalopathy.Expert review of anti-infective therapy · 2009Review
- Interactions of pluronic block copolymers on P-gp efflux activity: experience with HIV-1 protease inhibitors.Journal of pharmaceutical sciences · 2008Article
- MRP (ABCC) transporters-mediated efflux of anti-HIV drugs, saquinavir and zidovudine, from human endothelial cells.Experimental biology and medicine (Maywood, N.J.) · 2008Article
- Inhibition of placental P-glycoprotein: impact on indinavir transfer to the foetus.British journal of clinical pharmacology · 2008Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeTo quantitatively characterize the drug efflux interactions of various HIV-1 protease inhibitors in an in vitro model of the blood-brain barrier (BBB) and to compare that with HIV-1 protease inhibitor stimulated P-glycoprotein (P-gp)-ATPase activity.
methodsCellular accumulation of the P-gp sensitive probe, rhodamine 123 (R123), and the mixed P-gp/multidrug resistance-associated protein (MRP) probe, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF), were evaluated in primary cultured bovine brain microvessel endothelial cells (BBMEC) in the presence of various concentrations of HIV-1 protease inhibitors. The potency (IC50) and efficacy (Imax) of the drugs in the cell accumulation assays for P-gp and/or MRP was determined and compared to activity in a P-gp ATPase assay.
resultsFor R123 (P-gp probe), the rank order potency for inhibiting R123 accumulation in the BBMEC was saquinavir=nelfinavir>ritonavir=amprenavir>indinavir. This correlated well with the rank order affinity in the P-gp ATPase assay. The rank order potency for MRP-related drug efflux transporters, was nelfinavir>ritonavir>saquinavir>amprenavir>indinavir.
conclusionsHIV-1 protease inhibitors potently interact with both P-gp and MRP-related transporters in BBMEC. Characterization of the interactions between the HIV-1 protease inhibitors and drug efflux transporters in brain microvessel endothelial cells will provide insight into potential drug-drug interactions and permeability issues in the BBB.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.